Chronic HIV Infection Enhances the Responsiveness of Antigen Presenting Cells to Commensal Lactobacillus

Abstract

Chronic immune activation despite long-term therapy poses an obstacle to immune recovery in HIV infection. The role of antigen presenting cells (APCs) in chronic immune activation during HIV infection remains to be fully determined. APCs, the frontline of immune defense against pathogens, are capable of distinguishing between pathogens and non-pathogenic, commensal bacteria. We hypothesized that HIV infection induces dysfunction in APC immune recognition and response to some commensal bacteria and that this may promote chronic immune activation. Therefore we examined APC inflammatory cytokine responses to commensal lactobacilli. We found that APCs from HIV-infected patients produced an enhanced inflammatory response to Lactobacillus plantarum WCFS1 as compared to APCs from healthy, HIV-negative controls. Increased APC expression of TLR2 and CD36, signaling through p38-MAPK, and decreased expression of MAP kinase phosphatase-1 (MKP-1) in HIV infection was associated with this heightened immune response. Our findings suggest that chronic HIV infection enhances the responsiveness of APCs to commensal lactobacilli, a mechanism that may partly contribute to chronic immune activation.

Early Mucosal Sensing of SIV Infection by Paneth Cells Induces IL-1β Production and Initiates Gut Epithelial Disruption

“…The occurrence of aberrant host immune responses to commensal bacteria has been reported during chronic inflammatory conditions such as inflammatory bowel diseases (IBD) [39] and recently in acute Toxoplasma gondii infection [22] . Aberrant inflammatory response to commensal bacteria by peripheral monocytes of individuals with chronic HIV infection has been reported [40] . It is not known whether acute HIV infection might obfuscate the host's ability to distinguish between pathogen and commensals.…”

“…It is not known whether acute HIV infection might obfuscate the host's ability to distinguish between pathogen and commensals. Aberrant immune responses to commensal bacteria during chronic HIV infection may be attributed to increased microbial translocation [2] , immune activation of antigen presenting cells [40] , [41] , and increased TLR2 and TLR4 expression [42] , [43] . However, there have been no known studies that have interrogated gut mucosal immune responses to commensal bacteria in the context of early HIV infection.…”

Innate and Adaptive Immune Regulation During Chronic Viral Infections

“…In line with these observations, chronic HCV infection also promotes hyperresponsive macrophages, including Kupffer cells, contributing to the chronic liver inflammation that is characteristic of chronic HCV infection (41, 42). Finally, macrophages treated with HIV and antigen-presenting cells isolated from HIV-infected patients show hyperresponsiveness to unrelated TLR ligands and commensal bacteria, respectively (43, 44). …”

SIV‐infection‐driven changes of pattern recognition receptor expression in mesenteric lymph nodes and gut microbiota dysbiosis

“…Under dysbiotic conditions, there is increased trafficking of commensal bacteria to the mLN where they induce T‐cell responses and IgA production . This might, in part, contribute to heightened sensitivity of HIV‐infected patients to commensal microbes . It is tempting to speculate that dysbiosis in the gut during SIV infection results in increased trafficking of commensal microbiota to the mLN exacerbating SIV‐induced inflammation in the mLN, and potentially further disrupting gut communities.…”